《生命科学》 2026, 38(1): 36-45
代谢功能障碍相关脂肪性肝病动物模型研究进展
摘 要：
代谢功能障碍相关脂肪性肝病（metabolic dysfunction-associated fatty liver disease，MAFLD）是一类与代谢功能障碍密切相关的肝脏疾病谱系，其发病机制复杂且仍未完全阐明。动物模型是探索MAFLD发生发展机制、评估干预策略与药物转化的基础工具。本文综述并比较了当前常用的MAFLD动物模型，包括饮食诱导模型、药物/化学诱导模型、基因工程模型及非人灵长类模型，重点讨论了各模型的配方细节、诱导时程、能再现的人类病理与代谢特征及局限性。文章还提出了选模建议以提高研究可重复性与转化价值，为MAFLD基础与转化研究提供实用参考。
通讯作者：马春丽 , Email:ma200614127@126.com 包玉龙 , Email:472689713@qq.com
Abstract:
Metabolic dysfunction-associated fatty liver disease (MAFLD) represents a global health challenge with a complex and incompletely understood pathogenesis. Animal models serve as indispensable tools for elucidating the mechanisms underlying MAFLD development, evaluating potential therapeutic interventions, and facilitating drug translation. This review aims to systematically summarize and compare the currently available animal models of MAFLD, providing practical guidance for selecting appropriate models in basic and translational research. We categorize MAFLD animal models into four main types: diet-induced models, drug/chemical-induced models, genetically engineered models, and non-human primate (NHP) models. Each model type is discussed in detail, focusing on formulation specifics, induction timelines, reproducible human pathological and metabolic features, and inherent limitations. Diet-induced models, particularly high-fat diets (HFD), are highlighted for their ability to closely mimic human MAFLD pathology, including obesity, insulin resistance, and hepatic steatosis. Drug/chemical-induced models, such as the methionine-choline deficient (MCD) diet and carbon tetrachloride (CCl4) treatment, offer rapid induction of hepatic inflammation and fibrosis but often lack metabolic features observed in human MAFLD. Genetically engineered models provide insights into specific gene functions and pathways but may not fully recapitulate the polygenic and environmental interactions characteristic of human MAFLD. NHP models, due to their close physiological and metabolic resemblance to humans, offer unparalleled translational potential but are limited by high costs and ethical considerations. The selection of an appropriate MAFLD animal model should be guided by the specific research objectives, taking into account factors such as the desired disease stage (e.g., simple steatosis vs. fibrosis), metabolic features, induction timeline, and cost-effectiveness. For mechanistic studies focusing on metabolic pathways, HFD models or genetically engineered models may be preferred. For drug efficacy screening, models that rapidly induce hepatic inflammation and fibrosis, such as MCD combined with CCl4, may be more suitable. NHP models should be reserved for high-value translational studies where close physiological resemblance to humans is critical. Standardization of reporting practices, including detailed descriptions of animal strains, diets, induction protocols, and outcome measures, is essential to enhance the reproducibility and comparability of research findings. Additionally, the use of multiple complementary models is encouraged to capture the heterogeneous nature of MAFLD and strengthen the validity of research conclusions. In conclusion, this review provides a comprehensive overview of the current landscape of MAFLD animal models, highlighting their strengths, limitations, and optimal applications. By adhering to the proposed recommendations, researchers can enhance the rigor, reproducibility, and translational value of their MAFLD studies, ultimately accelerating the development of effective therapeutic strategies for this global health burden.
Communication Author：MA Chun-Li , Email:ma200614127@126.com BAO Yu-Long , Email:472689713@qq.com
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